Abstract 3055: Associations of the mucosal microbiome and circulating bile acids with colorectal adenoma among average-risk women
Authors: Maria F. Gomez, Doratha A. Byrd, Stephanie R. Hogue, Jessica R. Burns, Nathan Smith, Joshua Sampson, Erikka Loftfield, Andrew Warner, Casey Dagnall, Kristine Jones, Belynda Hicks, Yunhu Wan, Youngchul Kim, Jin Xu, Rashmi Sinha, Emily Vogtmann
Journal: Cancer Research (2023)

Abstract Background: The gut microbiome (GM) and the metabolites it produces and regulates, such as bile acids (BAs), may act individually or interact to influence colorectal cancer development. We used data from a multi-center screening study to investigate the associations of the normal colon tissue microbiome and circulating BAs with colorectal adenoma. Methods: We used data from the multi-center Colorectal Neoplasia Screening with Colonoscopy in Average-Risk Women Regional Navy/Army Medical Centers study (CONCeRN), comprising women undergoing complete colonoscopies. We individually matched women with adenoma (n=165 cases) to those without adenoma (n=311 controls). We extracted DNA using the Animal Tissue DNA Extraction Kit (AutoGene) and sequenced the V4 region of the 16S rRNA gene to characterize normal colonic mucosal bacteria, including alpha and beta diversity, taxonomic abundance, and co-abundance groups (CAGs). Fasting serum collected before colonoscopy underwent targeted quantitative liquid chromatography-tandem mass spectrometry to measure 13 primary and secondary BAs. We used multivariable conditional logistic regression, partial Pearson’s correlations, and linear regression to estimate interrelationships among the GM, BAs, and adenoma. Results: Multiple genera were statistically significantly associated with adenomas. For example, for the centered log-ratio transformed relative abundance of Phascolarctobacterium, Parvimonas, and Porphymonas, the ORs (95% CIs) were 0.75 (0.60-0.95, P=0.02), 0.71 (0.55-0.92; P=0.01), and 0.67 (0.49-0.93; P=0.02), respectively. A CAG comprising phylum Firmicutes, Actinobacteria, Proteobacteria, and Fusobacteria was less abundant among cases than controls (log2folddiff=-0.80, P=0.002). Alpha and beta diversity associations were close to null and not statistically significant. However, alpha diversity metrics were inversely associated with primary BAs [e.g., for Shannon (R2=-0.13, P=0.01)] and positively associated with secondary BAs [e.g., for Shannon (R2=0.16, P=0.001)]. Though no circulating BAs were statistically significantly associated with adenomas, those in the highest relative to lowest tertile of taurine-conjugated (TC) BAs, primary BAs, and secondary BAs had a 44% (95% CI: 0.85-2.46), 24% (95% CI: 0.73-2.12), and 11% (95% CI: 0.61-2.01) higher odds of adenoma, respectively. We found that TCBAs, primary BAs, and secondary BAs were inversely associated with the abundance of Parvimonas [e.g., for TCBAs (R2=-0.11, P=0.02)] and Porphyromonas [e.g., for TCBAs (R2=-0.11, P=0.02)]. Conclusions: We found short-chain fatty acid-producing and oral-originating bacteria were inversely associated with adenomas. Our oral bacteria findings are contrary to findings from prior studies. Our findings suggest potential interrelationships among the GM and BAs in adenoma development. Citation Format: Maria F. Gomez, Doratha A. Byrd, Stephanie R. Hogue, Jessica R. Burns, Nathan Smith, Joshua Sampson, Erikka Loftfield, Andrew Warner, Casey Dagnall, Kristine Jones, Belynda Hicks, Yunhu Wan, Youngchul Kim, Jin Xu, Rashmi Sinha, Emily Vogtmann. Associations of the mucosal microbiome and circulating bile acids with colorectal adenoma among average-risk women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3055.